Alzheimer's disease (AD) is a progressive neurodegenerative disease. It is prevalent among the elderly, affecting approximately 4 million Americans. Alzheimer's is a heterogeneous disease involving a number of components, including genetics. Although the accumulation of beta-amyloid peptide (AB) has been associated with both familial and sporadic forms of Alzheimer's, our current understanding of the role of AB and the mechanisms leading to the decline of cognitive function and neuronal loss are speculative. Transgenic mouse lines that over express AB peptides develop amyloid plaques and show age-related memory deficits have been created. Unfortunately, these mouse models for AD do not result in progressive neuronal loss as seen in humans. Whether this is due to species differences between mouse and human neurons can now be addressed directly by examining the fate of human neural cells transplanted into these AD mouse models. The ability to identify, isolate and expand human neural stem cells provides the opportunity to generate well-characterized cells for transplantation. In vivo properties of these cells have been extensively tested in the experimental NOD-Scid xenogeneic transplant mouse system. The striking features of the human CNS-SC is their capacity to engraft, migrate within the brain, and phenotypically differentiate into the three major cell types, neurons, astrocytes, and oligodendrocytes. Here we propose to examine the fate of human CNS-SC derived neural cells in the mouse models that recapitulate features of AD to assess the utility of neural cell transplants in the treatment of AD. Moreover, one can envision that these stem cells by their very biological property could produce and replace lost or dysfunctional neurons. The objectives of this grant are to test human neural stern cells as candidate therapeutics for the treatment of Alzheimer's disease. [unreadable] [unreadable] [unreadable]